Seizures associated with a known mutation and seizuresusceptible inbred strains are well documented in mice, however, seizures in the FVB strain have not been evaluated. Affected unmanipulated FVB/N (n=5) and transgenic FVB/N mice generated using 9 different unrelated transgenic constructs (n=63), were submitted for pathologic examination. Observations made during seizure presentation in 12 of 68 mice included facial grimace, chewing automatism, ptyalism with matting of the fur of the ventral neck and/or forelegs, and clonic convulsions which frequently progressed to tonic convulsions and death. Gross pathologic examination was nonremarkable. Microscopic findings were limited to the brain and liver. In all mice, acute neuronal necrosis was present in the cerebral cortex, hippocampus, and thalamus. A concurrent astrocyte hypertrophy as evidenced by an increase in glial fibrillary acidic protein staining was detected. Acute coagulative necrosis of centrilobular hepatocytes was present in the liver of some cases (19/68). No infectious agents were detected in selected brain specimens submitted for electron microscopy or in brain and liver specimens evaluated using a modified Steiner stain. Cytopathologic effect was not observed in 3T3 and BHK21 cell lines inoculated with affected brain and liver specimens. The ischemic neuronal necrosis observed in these mice is consistent with lesions associated with status epilepticus in man. The hepatocellular changes are interpreted to be agonal and associated with terminal hypoxia in seizuring animals. Our studies provide evidence of a previously unrecognized, often lethal, epileptic syndrome in FVB mice which may have a major impact upon transgenic research and other disciplines using this mouse strain.